What goes up must comedown: prevalence rates, characteristics, and coping strategies concerning MDMA aftereffects.

RATIONALE: MDMA is increasingly being studied for therapeutic applications, yet the prevalence and characteristics of post-acute negative effects remain debated.

OBJECTIVES

We aimed to characterize MDMA's post-acute negative effects, including prevalence and symptom profile among recreational users. Given preclinical work and limited human evidence suggesting that certain supplements and antidepressants may mitigate MDMA's negative effects, we also assessed the use of these substances as coping strategies.

METHODS

We conducted a cross-sectional online survey of 497 MDMA-experienced participants recruited from Prolific. The survey assessed post-acute negative effects prevalence, timing, and duration; post-acute side effects; emotional changes, suicidal ideation; and intentional use of supplements or antidepressants to manage symptoms. We compared characteristics of post-acute side effects between MDMA users who self-reported ever experiencing a negative post-acute MDMA experience (colloquially known as a 'comedown') and those who did not.

RESULTS

74.5% of participants reported experiencing a period of post-acute negative effects at least once, with onset occurring approximately 24 hours post-ingestion and lasting an average of 40 hours. The most common symptoms were fatigue (88.1%), difficulty concentrating (85.7%), restlessness (82.9%), and headache (79.7%). 14.6% of post-acute negative effects experiencers endorsed passive suicidal ideation and 6.2% endorsed active suicidal ideation. Regarding coping strategies, 30.3% reported using supplements (most commonly N-acetyl-cysteine, acetyl-L-carnitine, and magnesium) and 5.1% reported using antidepressants, with moderate perceived helpfulness.

CONCLUSIONS

Post-acute negative effects of MDMA appear prevalent among recreational users in a cross-sectional sample, characterized by fatigue, negative affect, and elevated suicidal ideation. These findings highlight post-acute risks that warrant further investigation.